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PRECIS Nailfold capillary abnormalities are associated with primary open-angle glaucoma (POAG) and increased severity of global and central glaucomatous visual field (VF) loss. PURPOSE The purpose of this study was to investigate whether nailfold capillary abnormalities are associated with POAG and the severity of glaucomatous VF loss. MATERIALS AND METHODS A cross-sectional study of 83 POAG cases and 40 controls was conducted. Nailfold capillaroscopy images were assessed by masked graders for dilated capillaries >50 μm, crossed capillaries, tortuous capillaries, hemorrhages, avascular zones >100 μm, capillary density, and capillary distribution. VF loss in glaucoma cases was quantified using mean deviation and mean central pattern standard deviation (PSD) from the worst-affected eye. RESULTS Logistic regression analyses of cases and controls showed that avascular zones [odds ratio (OR)=1.24; 95% confidence interval (CI): 1.06, 1.47; P=0.005], capillary density (OR=0.63; 95% CI: 0.46, 0.83; P

Background Compared to HIV-negative individuals, people living with HIV have a higher risk of malignant lymphoma. To what extent hematologists miss HIV testing opportunities among lymphoma patients (LP) in the Amsterdam University Medical Centers (UMC) is currently unknown. We quantified the HIV testing rate among LP and assessed factors influencing hematologists’ HIV testing behavior in LP at both Amsterdam UMC locations. Methods In this mixed-methods study, quantitative data from 2015 to 2019 from electronic health records of LP were retrospectively collected to assess both the HIV testing rate within three months around lymphoma diagnosis and the HIV positivity prevalence. An online survey among hematologists and semi-structured interviews among hematologists and authors of hematology guidelines were conducted. Results Data from 656 LP and 21 hematologists who responded to the survey out of 40 were used. Interviews were held with four hematologists and two authors of hematology guidelines. The HIV testing rates were 56.4% and 57.6%, and the HIV positivity prevalences were 0.8% and 0.9% for both locations. Eighty-five percent (18/21) of hematologists indicated they often offered an HIV test to LP in the past year, and 42% (9/21) revealed HIV testing in LP is often discussed in their department. The type of lymphoma, lack of awareness regarding HIV testing recommendations in LP, low perceived risk of HIV among LP because of older age, and lack of guidelines recommending universal HIV testing regardless of lymphoma type, each influenced hematologists’ HIV testing behavior. Conclusion Our results show routine HIV testing among LP and hematologists’ attitudes and knowledge towards testing at the Amsterdam UMC are suboptimal, despite HIV testing being recommended in most lymphoma guidelines. This highlights the need for interventions to improve hematologists’ behavior towards testing, such as education, as well as expansion and enhanced implementation of the hematology guidelines.

Aim of Study: The use of extracorporeal membrane oxygenation (ECMO) has increased as a result of technological developments and the expansion of indications. Relatedly, the number of patients undergoing surgery during ECMO is also rising, at least in the adult population. Little is known on surgery in children during ECMO-therapy. We therefore aimed to assess the frequencies and types of surgical interventions in neonatal and pediatric patients on ECMO and to analyze surgery-related morbidity and mortality.Methods: We retrospectively collected information of all patients on ECMO over a 10-year period in a single tertiary and designated ECMO-center, excluding patients undergoing cardiac surgery, and correction of congenital diaphragmatic hernia. Chi-squared test and Mann-Whitney U test were used to analyze data.Main Results: Thirty-two of 221 patients (14%) required surgery when on ECMO. Common interventions were thoracotomy (32%), laparotomy (23%), fasciotomy (17%), and surgical revision of ECMO (15%). Complications occurred in 28 cases (88%), resulting in a 50% in-hospital mortality rate. Surgical patients had a longer ICU stay and longer total hospital stay compared to those not receiving surgery during ECMO. No significant difference in mortality was found when comparing surgical to non-surgical patients (50 vs. 41%).Conclusions: Approximately one in seven neonatal or pediatric patients required surgical intervention during ECMO, of whom almost 90% developed a complication, resulting in a 50% mortality rate. These results should be taken into account in counseling.

Ocular surface changes and blink abnormalities are well-established in Parkinson's disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson's disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson's disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson's disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson's disease, ten were male and the mean age was 65.5±8.6years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson's disease (7.56±2.4mm/mm2) compared with controls (15.91±2.6mm/mm2) (p

Background and Objective. To determine if using a multi-input deep learning approach in the image analysis of optical coherence tomography (OCT), OCT angiography (OCT-A), and colour fundus photographs increases the accuracy of a CNN to diagnose intermediate dry age-related macular degeneration (AMD). Patients and Methods. Seventy-five participants were recruited and divided into three cohorts: young healthy (YH), old healthy (OH), and patients with intermediate dry AMD. Colour fundus photography, OCT, and OCT-A scans were performed. The convolutional neural network (CNN) was trained on multiple image modalities at the same time. Results. The CNN trained using OCT alone showed a diagnostic accuracy of 94%, whilst the OCT-A trained CNN resulted in an accuracy of 91%. When multiple modalities were combined, the CNN accuracy increased to 96% in the AMD cohort. Conclusions. Here we demonstrate that superior diagnostic accuracy can be achieved when deep learning is combined with multimodal image analysis.

PurposeTo determine whether vessel density (VD) as measured by optical coherence tomography angiography (OCT-A) provide insights into retinal and choriocapillaris vascular changes with ageing and intermediate dry age related macular degeneration (AMD).MethodsSeventy-five participants were recruited into three cohorts; young healthy (YH) group, old healthy (OH) and those at high-risk for exudative AMD. Raw OCT and OCT-A data from TOPCON DRI OCT Triton were exported using Topcon IMAGENET 6.0 software, and 3D datasets were analysed to determine retinal thickness and vessel density.ResultsCentral macular thickness measurements revealed a trend of overall retinal thinning with increasing age. VD through the full thickness of the retina was highest in ETDRS sector 4 (the inferior macula) in all the cohorts. Mean VD was significantly higher in the deep capillary plexus than the superficial capillary plexus in all ETDRS sectors in all cohorts but there was no significant difference noted between groups. Choriocapillaris VD was significantly lower in all ETDRS sectors in the in the AMD group compared with the YH and the OH groups.ConclusionsRetinal vessel density maps, derived from the retinal plexi are not reliable biomarkers for assessing the ageing macular. Our non-proprietary analysis of the vascular density of the choriocapillaris revealed a significant drop off of VD with age and disease but further work is required to corroborate this finding. If repeatable, choriocapillaris VD may provide a non-invasive biomarker of healthy ageing and disease.Brief SummaryIn this manuscript, we have studied the potential of retinal vessel density as measured by optical coherence tomography angiography (OCT-A), as a biomarker for detection of high-risk of developing exudative age-related macular degeneration (AMD).

Previous reports of ocular abnormalities in Huntington’s disease (HD) have detailed eye movement disorders. The objective of this case–control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 μm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R 2 = −0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R 2 = −0.71, p = 0.002), and motor scores (R 2 = −0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber’s hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.

Type 1 sialidosis is a metabolic storage disorder characterised by the accumulation of sialylated oligosaccharides. The condition is also known as macular cherry-red spot and myoclonus syndrome due to the characteristic macular appearance in affected individuals. This case outlines the presentation of a patient with type 1 sialidosis, including ophthalmological assessment with retinal photography and spectral domain optical coherence tomography (OCT). OCT scans showed thickening of the perimacular and peripapillary retinal nerve fibre layer, thought to be due to the abnormal accumulation of metabolic products. The cherry-red spot appearance is due to the normal appearing macula being seen in contrast to the abnormally pale surrounding, thickened retinal nerve fibre layer.

Objectives: Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands.Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior.Results: Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results.Conclusions: We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.

Item does not contain fulltext STUDY QUESTION: What is the percentage of overtreatment, i.e. fertility treatment started too early, in couples with unexplained infertility who were eligible for tailored expectant management? SUMMARY ANSWER: Overtreatment occurred in 36% of couples with unexplained infertility who were eligible for an expectant management of at least 6 months. WHAT IS KNOWN ALREADY: Prognostic models in reproductive medicine can help to identify infertile couples that would benefit from fertility treatment. In couples with unexplained infertility with a good chance of natural conception within 1 year, based on the Hunault prediction model, an expectant management of 6-12 months, as recommended in international fertility guidelines, prevents unnecessary treatment. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study in 25 participating clinics, with follow-up of all couples who were seen for infertility in 2011-2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 9818 couples were seen for infertility in the participating clinics. Couples were eligible to participate if they were diagnosed with unexplained infertility and had a good prognosis of natural conception (>30%) within 1 year based on the Hunault prediction model. Data to assess overtreatment were collected from medical records. Multilevel regression analyses were performed to investigate associations of overtreatment with patient and clinic characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Five hundred and forty-four couples eligible for expectant management were included in this study. Among these, overtreatment, i.e. starting medically assisted reproduction within 6 months, occurred in 36%. The underlying quality indicators showed that in 34% no prognosis was calculated and that in 42% expectant management was not recommended. Finally, 16% of the couples for whom a correct recommendation of expectant management for at least 6 months was made, started treatment within 6 months anyway. Overtreatment was associated with childlessness, higher female age and a longer duration of infertility. No associations between overtreatment and clinic characteristics were found. LIMITATIONS, REASONS FOR CAUTION: The response rate was low compared with other fertility studies. Evaluation of possible selection bias showed that responders had a higher socio-economic status than non-responders. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that developing and publishing guideline recommendations on tailored expectant management (TEM) is not enough and that overtreatment still occurs frequently. Future research should focus on tailored efforts to implement guideline recommendations on TEM. STUDY FUNDING/COMPETING INTERESTS: Supported by Netherlands Organisation for Health Research and Development (ZonMW). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none. TRIAL REGISTRATION NUMBER: www.trialregister.nl NTR3405.

A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p < 0.001)]. Macular thickness was significantly greater (p < 0.005) in five of the nine macular regions. The increase in macular thickness was due to the increased prevalence of epiretinal membranes in the myotonic dystrophy patient group (p = 0.0002): 48.2 % of myotonic dystrophy patient eyes had evidence of epiretinal membrane, compared with 12.5 % of control eyes. Examination revealed that 56.7 % of myotonic dystrophy patients had an epiretinal membrane in at least one eye. Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity.

Item does not contain fulltext STUDY QUESTION: How does the cost-effectiveness (CE) of immediate IVF compared with postponing IVF for 1 year, depend on prognostic characteristics of the couple? SUMMARY ANSWER: The CE ratio, i.e. the incremental costs of immediate versus delayed IVF per extra live birth, is the highest (range of euro15 000 to >euro60 000) for couples with unexplained infertility and for them depends strongly on female age and the duration of infertility, whilst being lowest for endometriosis (range 8000-23 000) and, for such patients, only slightly dependent on female age and duration of infertility. WHAT IS KNOWN ALREADY: A few countries have guidelines for indications of IVF, using the diagnostic category, female age and duration of infertility. The CE of these guidelines is unknown and the evidence base exists only for bilateral tubal occlusion, not for the other diagnostic categories. STUDY DESIGN, SIZE, DURATION: A modelling approach was applied, based on the literature and data from a prospective cohort study among couples eligible for IVF or ICSI treatment, registered in a national waiting list in The Netherlands between January 2002 and December 2003. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 5962 couples was included. Chances of natural ongoing pregnancy were estimated from the waiting list observations and chances of ongoing pregnancy after IVF from follow-up data of couples with primary infertility that began treatment. Prognostic characteristics considered were female age, duration of infertility and diagnostic category. Costs of IVF were assessed from a societal perspective and determined on a representative sample of patients. A cost-effectiveness comparison was made between two scenarios: (I) wait one more year and then undergo IVF for 1 year and (II) immediate IVF during 1 year, and try to conceive naturally in the following year. Comparisons were made for strata determined by the prognostic factors. The final outcome was a live birth. MAIN RESULTS AND THE ROLE OF CHANCE: The gain in live birth rate of the immediate IVF scenario versus postponed IVF increased with female age, and was independent from diagnostic category or duration of infertility. By contrast, the corresponding increase in costs primarily depended on diagnostic category and duration of infertility. The lowest CE ratio was just below euro10 000 per live birth for endometriosis from age 34 onwards at 1 year duration. The highest CE ratio reached euro56 000 per live birth for unexplained infertility at age 30 and 3 years duration, dropping to values below euro 30 000 per live birth from age 32 onwards. It reached values below euro20 000 per live birth with 3 years duration at age 34 and older. The CE ratio was in between for the three other diagnostic categories (i.e. Male infertility, Hormonal and Immunological/Cervical). LIMITATIONS, REASONS FOR CAUTION: We applied estimates of chances with IVF, excluding frozen embryos, for which we had no data. Therefore, we do not know the effect of frozen embryo transfers on the CE. WIDER IMPLICATIONS OF THE FINDINGS: The duration of infertility at which IVF becomes cost-effective depends, firstly, on the level of society's willingness to pay for one extra live birth, and secondly, given a certain level of willingness to pay, on the woman's age and the diagnostic category. In current guidelines, the chances of a natural conception should always be taken into account before deciding whether to start IVF treatment and at which time. STUDY FUNDING/COMPETING INTEREST(S): Supported by Netherlands Organisation for Health Research and Development (ZonMW, grant 945-12-013). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none.

Structural and thermal data were obtained for a novel hemihydrate of 6-mercaptopurine. The hemihydrate shows increased solubility and bioavailability when compared to the monohydrate form, better stability against conversion in aqueous media than the anhydrate form, and a dehydration temperature of 240 °C, the highest of any known hydrate crystal.

Background Previous reports of ocular abnormalities in Huntington’s disease (HD) have detailed eye movement disorders but not whether the nerve fibre layer at the back of the eye is affected. This layer has been shown to be thinned in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Aims The objective of this case-control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). Methods A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Results Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 μm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R (2) = −0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R (2) = −0.71, p = 0.002), and motor scores (R (2) = −0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Conclusions Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber’s hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.

In April 1996, an outbreak of toxic polyneuropathy in cats occurred in the Netherlands. All cats had been fed one of two brands of dry cat food from one manufacturer. Chemical analyses of these foods, stomach contents, and liver and kidney of affected cats revealed contamination with the ionophor salinomycin. Epidemiologic and clinical data were collected from 823 cats, or about 1% of the cats at risk. In 21 affected cats, postmortem examination was performed. The affected cats had acute onset of lameness and paralysis of the hindlimbs followed by the forelimbs. Clinical and pathologic examination indicated a distal polyneuropathy involving both the sensory and motor nerves.

Myotonic dystrophy type 1 is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. In the eye it commonly causes ptosis and cataracts and has been associated with retinal pigmentary changes. In a case control study of 30 patients not selected for eye symptoms and 28 age matched controls, we performed a comprehensive screen of the eye including optical coherence tomography of macula and retinal nerve fibre layer, visual acuity and colour vision, pupil assessment, visual fields, slit lamp, intra ocular pressure, dilated fundal examination and retinal photography. We also assessed patients’ CTG repeat size, age, 6 min walk and motor impairment rating scale (MIRS). We examined 59 eyes in 30 patients (one patient had recent eye surgery and was unable to be examined in that eye) and 56 eyes in 28 controls. Twenty-six eyes (44%) in 18 (60%) myotonic dystrophy patients showed evidence of epiretinal membranes (ERM) compared with just 4 (7%) eyes in 4 controls (14%); p